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Abstract

We
report three cases of patients with acute liver injury induced by
weight-loss herbal supplements. One patient took Hydroxycut while the
other two took Herbalife supplements. Liver biopsies for all patients
demonstrated findings consistent with drug-induced acute liver injury.
To our knowledge, we are the first institute to report acute liver
injury from both of these two types of weight-loss herbal supplements
together as a case series. The series emphasizes the importance of
taking a cautious approach when consuming herbal supplements for the
purpose of weight loss.

INTRODUCTION

We have seen a significant increase in the popularity and usage of over the counter herbal supplements over the past few years[1].
Unfortunately, the majority of these herbal supplements are not
regulated by drug administrations worldwide. Many herbal supplements
contain compounds that carry potentially severe side effects including
hepatotoxicity. We report three cases of acute liver injury induced by
weight-loss herbal supplements. Hydroxycut (MuscleTech, Mississauga,
Ontario, Canada) (case 1) and Herbalife (Herbalife, Los Angeles, USA)
(cases 2 and 3) supplements were the suspected culprits of acute liver
injury. Hydroxycut is a popular dietary supplement consisting of a
variety of herbal mixtures that claims to enhance the weight loss
process[2].
Acute liver injury associated with Hydroxycut use has been previously
reported, but only one case had liver biopsy data showing cholestasis
and portal inflammation[3-6].
Similarly, Herbalife weight-loss dietary products are popular
supplements consisting of a variety of herbal mixtures that claim to
facilitate weight reduction[7].
Cases of acute liver injury after consumption of Herbalife products
have been previously reported, with two patients developing fulminant
liver failure requiring liver transplantation. The first patient
survived while the second died[8-11]. In all of our cases, we were able to demonstrate drug-induced acute liver injury on liver biopsy specimens.

CASE REPORT

Case 1

A
31-year-old woman presented to our hospital complaining of 2-wk history
of fatigue, jaundice, and nausea. She denied any prior medical or
surgical conditions, family history of liver disease, and acetaminophen
or prescription medication use. She further denied history of blood
transfusion, tattoo, alcohol use, or recreational drug use. She had been
taking Hydroxycut for one year to enhance her weight loss. She had been
taking the recommended dose of 2 tablets twice a day.

The
patient’s liver function tests peaked 4 d after admission with serum
AST level of 1613 U/L, ALT level of 1227 U/L, serum alkaline phosphatase
of 268 U/L, serum TB of 10.5 mg/dL, and INR staying at 1.3 I/U. She did
not develop evidence of hypoglycemia or portal-systemic encephalopathy.
Her jaundice and scleral icterus resolved over the following 2-wk. Her
liver tests gradually improved within the following few months.

Case 2

A
37-year-old woman presented to our hospital with a 1-mo history of
diffuse abdominal pain, mild nausea, and painless jaundice. She denied
any past medical or surgical history, family history of liver disease,
or any alcohol or illicit substance abuse. She admitted that she had
been taking Herbalife dietary supplements for the past 3-mo in an
attempt to lose weight. Her Herbalife regimen consisted of the Formula
One Nutritional Shake Mix, the Multivitamin Complex, the Cell Activator,
the Cell-U-Loss, the Herbal Concentrate Original, and the Total Control
formula.

The patient was afebrile with normal
vital signs on presentation. Her physical exam was noticeable for
bilateral scleral icterus and generalized jaundice. Her abdominal exam
revealed a non-tender, non-distended abdomen with no stigmata of liver
disease. Initial laboratory studies were significant for an AST level of
2199 U/L, serum ALT level of 2068 U/L, serum alkaline phosphatase of
185 U/L, and TB of 15.3 mg/dL. All other laboratory values, including
amylase, lipase, and INR, were within normal limits. Given these lab
abnormalities, the patient was admitted to the hospital for further
work-up.

The
patient was treated supportively with fluids and nutrition. Her liver
tests steadily declined from the day of admission and on hospital day 8
(day of discharge) her liver tests revealed a AST level of 1788 U/L, ALT
level of 1501 U/L, and serum alkaline phosphatase of 183 U/L. The only
laboratory value to increase was the patient's serum TB, which was at
29.9 mg/dL on discharge. The patient did not develop encephalopathy,
hypoglycemia, or any other complications. The patient was followed for
several months, throughout which her symptoms continued to improve.

At
her 2-mo follow-up, the patient's icterus and jaundice had resolved
completely. Her labs at this time showed a serum AST level of 51 U/L,
serum ALT level of 43 U/L, serum alkaline phosphatase of 65 U/L, and
serum TB of 1.1 mg/dL.

Case 3

A
53-year-old previously healthy woman presented with a 3-wk history of
painless jaundice and pruritus. She denied any family history of liver
disease, or any alcohol or illicit substance abuse. She had not been
taking any new prescribed medications. On further questioning about
over-the-counter supplements she divulged a 4-mo history of consuming
various Herbalife weight loss products in the form of shakes, teas and
pills.

On physical exam the patient’s vital
signs were within normal limits. On general inspection she had scleral
icterus and jaundice, with evidence of excoriations. A 2-cm palpable
liver edge could be appreciated, that was tender to touch. There were no
other signs of chronic liver disease. Initial laboratory values
revealed a hepatocellular pattern of injury, with an AST of 1282 U/L,
ALT of 983 U/L, and alkaline phosphatase of 292 U/L, with a TB of 18.2
mg/dL. An ultrasound showed borderline hepatomegaly of 17-cm.

Liver biopsy was performed and showed cholestasis, consistent with drug induced hepatitis (Figure ​(Figure3).3). 2-mo after complete abstinence from the Herbalife supplements her jaundice resolved, as did her liver tests.

DISCUSSION

Acute
liver injury induced by over the counter weight-loss herbal supplement
Hydroxycut and Herbalife products have been reported previously[3-6,8-11].
These case reports were limited by the fact that liver biopsies were
performed in only a few patients, confirming clinical suspicions
histologically. In terms of our patients, all three had liver biopsy
performed and all showed some common morphological features including
diffuse lymphocytic infiltration of sinusoids and portal tracts, ductal
metaplasia and toxic necrosis. Some variations of morphological features
could be explained by predominance of intrinsic or idiosyncratic
mechanisms of hepatic injury, individual patient response to the
affecting drug and duration of injury. The patients’ liver biopsy
specimens were stained with periodic acid-Schiff (PAS) stain with
diastase. No hyaline globules were identified in any of the three cases.
The absence of histological findings and the fact that our patients had
no history of chronic obstructive pulmonary disease excluded diagnosis
of alpha-1-antitripsin deficiency in all three cases. Prussian blue and
copper stains did not reveal excessive iron or copper depositions in the
hepatocytes and Kupffer cells.

Only one
previous case of Hydroxycut-induced acute liver injury had reported
findings on liver biopsy. Although the most likely explanation for the
mechanism of liver injury caused by these herbal products is
idiosyncratic reaction, one of the ingredients in Hydroxycut, green tea
extract (Camellia sinensis), has been linked with acute liver injury in other over the counter weight-loss herbal supplements[12-20]. In fact, the weight-loss herbal supplement Exolise (Arkophama, Carros, France), which also contained C. sinensis, was withdrawn from the market because it was linked to multiple cases of liver injury[13].
Furthermore, several cases of hepatotoxicity were associated with
another herbal weight-loss supplement, Cuur (Scandinavian Clinical
Nutrition, Sweden), which also contains the ethanolic dry extract of
green tea (C. sinensis)[15]. Rechallenging patients with the same product led to hepatotoxicity, confirming the role of C. sinensis[12,16].
In all reported cases of acute liver injury induced by Hydroxycut,
patients’ liver function tests recovered over time following cessation
of the product. However, there have been cases of liver failure caused
by green tea extract C. sinensis, requiring orthotopic liver transplantation[13,16].

The
liver biopsy obtained in our patient who took Hydroxycut showed
multi-lobular necrosis consistent with acute toxic necrosis and
fulminant hepatitis. These findings are similar to the findings in
patients with liver injury associated with green tea extract C. sinensis, where prominent necrosis with inflammatory reaction is the hallmark presentation[15,16].

The exact mechanism of hepatotoxicity induced by Hydroxycut is unknown. However, as this product contains green tea extract C. sinensis,
it is possible that this may play a role in acute liver injury caused
by Hydroxycut. Prior investigation into the mechanism of hepatotoxicity
by green tea extract was inconclusive[21].
Others have hypothesized that a possible allergic reaction to the green
tea extract, contamination during the production of the extract or a
metabolic idiosyncrasy are possible mechanisms of liver injury in these
patients[16].

Both
of our patients took several Herbalife weight-loss herbal products
concurrently, similar to most of the previously reported cases of
hepatotoxicity due to Herbalife products[8-11].
Therefore, it is difficult to identify the exact ingredient or
mechanism that causes the liver injury, as in the previously documented
cases[8-11]. In a previously reported case, one investigator was able to isolate contamination with Bacillus subtilis, in which the bacterial supernatant caused dose-dependent increase of LDH leakage in HepG2 cells[8]. Although not commonly known as a human pathogen, B. subtiliis has been reported to cause food poisonings and a case of cholangitis in an immunocompromised patient[22-23].
Investigators have also suggested that another explanation for
hepatotoxicity due to Herbalife products could be secondary to locally
restricted contamination with chemicals such as softeners,
preservatives, flavor enhancers, pesticides, or heavy metals either
intentionally added during the production process or contained in the
unrefined raw herb extracts[24].

To date, Herbalife has refused to provide detailed analyses of their products’ composition and ingredients[25].
This contamination hypothesis could also explain the different patterns
of pathology seen on liver biopsy specimens previously observed in
patients with hepatotoxicity from Herbalife products as both
predominantly cholestatic injury pattern and acute hepatitis pattern
have been reported[8-11]. Our patients had findings consistent with acute hepatitis due to drug-induced liver injury on their liver biopsy specimens.

Due
to the obesity epidemic, the usage of weight-loss herbal supplements
has flourished. Green tea extract is one of the key components in many
of the over-the-counter weight-loss herbal supplements. Although
significant liver injury induced by herbal supplements taken for weight
loss purposes is a rare event, we cannot ignore the fact that there have
been multiple reported cases in the medical literature of
hepatotoxicity associated with weight-loss herbal supplements including
Hydroxycut and Herbalife products. Even though our patients successfully
recovered from the adverse reactions, we must bear in mind that the
hospitalization and medical care of these patients were associated with
significant cost and healthcare resource utilization, while there is no
evidence that herbal supplements can help with weight-loss[26].
We must also consider the impact on patients with underlying chronic
liver disease, in whom herbal weight loss medications could cause
worsening in their synthetic function and even fulminant failure. In May
of 2009, the US Food and Drug Administration warned consumers to
immediately stop using Hydroxycut products, citing linkage to liver
damage in one patient who died due to liver failure[27].
However, Hydroxycut products are currently still available in many
parts of the world. Likewise, Herbalife products are widely available
globally. Therefore, it is these authors’ view that closer monitoring of
patients taking weight-loss herbal supplements as well as tighter
regulation from government drug agencies is warranted. Furthermore, our
cases once again demonstrated the importance of questioning patients
regarding the usage of herbal or nutritional supplements at the time of
evaluation.

Abstract

Aloe
has been widely used in phytomedicine. Phytomedicine describes aloe as a
herb which has anti-inflammatory, anti-proliferative, anti-aging
effects. In recent years several cases of aloe-induced hepatotoxicity
were reported. But its pharmacokinetics and toxicity are poorly
described in the literature. Here we report three cases with
aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a
55-yr-old woman were admitted to the hospital for acute hepatitis. They
had taken aloe preparation for months. Their clinical manifestation,
laboratory findings and histologic findings met diagnostic criteria
(RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe
preparations, liver enzymes returned to normal level. Aloe should be
considered as a causative agent in hepatotoxicity.

INTRODUCTION

The
demand for dietary supplements has continually increased in recent
years as the concept of 'well being' widely spread in Korea. The market
value for dietary supplements in Korea was approximately 600 billion won
(600 million USD) in year 2005 (1), and personal spending was approximately 950,000 won (950 USD) per year in 2005 (2). One of the leading products in Korea's dietary supplements market is aloe.

Aloe
has been purported to have positive effects on wound healing, recovery
from burn injury, cell growth, and immune modulation. However, cases of
aloe-induced toxic hepatitis have been reported since 2005. In
particular, there have been one each in Germany (3), Turkey (4), and USA (5). In Switzerland (6),
10 cases of hepatotoxicity associated with dietary supplements from
Herbalife® products were reported. Although 2 of those 10 cases took
aloe preparation, the causality assessment between aloe and toxic
hepatitis could not be done due to multiple Herbalife® products.

CASE REPORTS

Case 1

A
57-yr-old female patient with a 2 month history of dyspepsia was
presented to our department. Past medical history and family history did
not reveal any significant disease. She also used drugs for arthralgia
intermittently for several years. She did not take any alcohol. She had
taken aloe tablets containing 250 mg of an extract of Aloe arborescens and 28.5 mg of an extract of Aloe vera (Fig. 1) for about 6 months prior to the admission. On admission, the patient's physical examination was normal.

Histopathological findings of the liver. (A) The portal area and lobular area show inflammatory cell infiltration (H&E, ×100). (B) The acidophilic body and ballooning cell change are noted (H&E, ×200).

Aloe
tablets was immediately discontinued. ALT was highest (926 IU/L) on the
12th day of admission and gradually decreased to 452 IU/L on the 25th
day of admission. ALT as well as total bilirubin gradually returned to
normal level over several weeks (Fig. 3).
Using the Roussel Uclaf Causality Assessment Method for determining
drug hepatotoxicity (RUCAM) scale, this case was scored as 'probable' (Table 1).
The type of liver injury was determined as 'hepatocellular' since R
ratio (serum activity of ALT/serum activity of AP) was 10 (7).

Case 2

A
62-yr-old female patient was presented to our department with a week
history of fatigue. Past medical history and family history did not
reveal any significant disease. The patient did not take any alcohol or
durgs. She had taken aloe powder containing 420 mg of an extract of Aloe vera (Fig. 1B)
for about 3 months prior to the admission. Physical examination
revealed jaundice on her sclera. She was the sales person of the aloe
product she was taking.

Aloe
extract was immediately discontinued. ALT gradually decreased to 452
IU/L which was lower than half of the peak value on the 17th day of
admission. When she was discharged ALT and AST were normal. We explained
to her about the aloe-induced hepatotoxity and advised not to take it
anymore. However, the patient started taking the same aloe extract again
1 month after her discharge from the hospital. A month later, follow-up
liver function test showed AST 477 IU/L, ALT 785 IU/L, and AP 165 IU/L (Fig. 4).
Since a hepatitis recurred after re-challenge of aloe extract, we could
confirm her diagnosis as aloe-induced toxic hepatitis. The RUCAM scale
was scored as 'definite' (Table 1). The type of liver injury was determined as 'hepatocellular' since R ratio was 39.

Case
2. Upon discontinuation of the oral aloe preparation, liver enzymes
returned to normal level. After re-challenge (arrow), liver enzymes go
up again.

Six months later, the
patient was presented to our department with a 2 week history of
jaundice. Laboratory test showed AST 752 IU/L, ALT 1,135 IU/L, AP 243
IU/L and total bilirubin 15.81 mg/dL. We recommended admission, but she
refused to be admitted and she never visited our hospital again.

Case 3

A
55-yr-old female patient was presented to our department with a 3 month
history of epigastric discomfort. Past medical history and family
history did not reveal any significant disease. The patient did not take
any alcohol or drugs. She had taken aloe extracts (Fig. 1)
for about 5 months prior to the admission. On admission, the patient's
physical examination was normal except mild tenderness on epigastric
area.

Aloe
extract was immediately discontinued. ALT was highest (666 IU/L) on the
2nd day of admission, and gradually decreased. ALT was 484 IU/L on her
discharge (on the 5th day of admission). After 4 days, she visited our
department for follow-up. Liver function test was normal at that time
(AST 29 IU/L, ALT 11 IU/L, AP 190 IU/L) (Fig. 5). The RUCAM scale was scored as 'probable' (Table 1). The type of liver injury was determined as 'hepatocellular' since R ratio was 11.

DISCUSSION

The
major driving force for the growth of the dietary supplements market is
the perception that 'they are safe because they are natural'. However,
the recently reported cases of hepatotoxicity induced by natural
substances (8) indicate that natural substances may not be entirely safe.

There are about 400 species of aloe. Among them, particularly aloe vera has been used in phytomedicine. There have been positive reports on aloe vera as anti-inflammatory, anticancer, analgesic, anti-aging as well as liver protective. But, clinical effectiveness of aloe vera was not sufficiently defined because there were no large and randomized studies (9). In 1994, Korea's National Institute of Safety Research conducted an experiment on the efficacy and toxicity of aloe (10). There was no difference of natural killer cell activity between the aloe vera
gel treated and control animals. To observe the toxicity of aloe gel,
rats were given the high dose aloe orally. Any adverse effects were not
detected in hematological test, serum biochemistry, and
histopathological examination.

There are no specific
tests or diagnostic criteria for herbinduced hepatic injury. Careful
history taking, laboratory finding, and histopathology are used to
diagnose it. The best way to determine causing agent is re-challenging.
But it is not ethical and not applicable. Instead, the RUCAM scale is
used (7, 11).

Since
patients usually do not regard dietary supplements as 'real' medicine,
they may fail to mention it when physicians query medication history.
Physicians should keep in mind that dietary supplements can be the cause
of hepatotoxicity when querying medication history, and should educate
the lay public.

There are three types of acute liver injury by drug or herb (12):
hepatocellular, cholestatic, and mixed type. Our cases are
characterized as hepatocellular; there is a predominant initial
elevation of the ALT level. There are two proposed pathogeneses of drug
induced liver disease (13):
direct toxicity and idiosyncratic mechanism. It is more likely that an
idiosyncratic immunological mechanism (hypersensitivity) is responsible
for the cases. A role for hypersensitivity is further supported by the
presence of eosinophilic granulocytes in the periportal fields seen in
the biopsy. Hypersensitivity to aloe has been described in humans (14), and the patch test or allergic skin test showed positive results (15).

Herb
induced liver injury is an important problem in clinical setting,
because it can be an etiology of undiagnosed acute hepatitis. However,
there are few available data about the incidence and clinical
manifestation of dietary supplements such as aloe. Our cases emphasize
that physicians should consider various dietary supplements as causative
agents for hepatotoxicity.

Abstract

In
the November 27, 2010 issue of the World Journal of Hepatology (WJH),
three case reports were published which involved patients who had
consumed various dietary supplements and conventional foods generally
marketed as weight loss products. The reference to Herbalife products as
contaminated and generally comparable to all dietary supplements or
weight loss products is not scientifically supported. The authors
provided an insufficient amount of information regarding patient
histories, concomitant medications and other compounds, dechallenge
results, and product specifications and usage. This information is
necessary to fully assess the association of Herbalife products in the
WJH case reports. Therefore, the article does not objectively support a
causal relationship between the reported cases of liver injury and
Herbalife products or ingredients.

TO THE EDITOR

In the November 27, 2010 issue of the World Journal of Hepatology (WJH),
three case reports were published which involved patients who had
consumed various dietary supplements and conventional foods generally
marketed as weight loss products. Case 1 involved a patient who did not
consume Herbalife products, while Cases 2 and 3 each reportedly consumed
various Herbalife products. Herbalife fundamentally disagrees with the
conclusions made by the authors with regard to any cause and effect
relationship related to the intake of Herbalife products. First,
Herbalife is not a single product and no unique suspect product or
ingredient has been implicated in this paper amongst the reported cases.
In addition, the authors arbitrarily compared cases involving the use
of a single product (Hydroxycut) with patients who consumed a group of
totally unrelated products produced by the company Herbalife. To bundle a
brand of products such as Herbalife with another company that sells
different products simply because they are all dietary supplements is
not valid. Finally, there are specific considerations, in regard to the
two patients who consumed Herbalife products, that would render many of
the observations and conclusions discussed by the authors as speculative
and unsubstantiated. The specific and factual points supporting these
views are further detailed below.

Case 2 describes a
37-year-old female who developed symptoms of abdominal pain, mild
nausea, and painless jaundice 1 mo prior to presenting at the hospital[1].
Several pertinent negatives were disclosed by the authors, including
autoimmune markers and viral serology. According to the authors, the
patient did not report any pre-existing medical conditions for which the
onset had preceded the use of Herbalife products. However, the
pathology assessment concluded that this patient’s biopsy result was
consistent with chronic liver disease, in which case Herbalife products
were thought to have had an additive effect. This opinion contradicts
repeated statements by the authors that acute liver injury in each case
report was due to the use of herbal weight loss products. In addition,
the etiology of the pre-existing condition was not identified by the
authors, and there was no discussion regarding the role of the condition
in the acute onset of her symptoms. Furthermore, the dosage and
frequency at which this patient consumed Herbalife products is unknown.
Finally, the inconsistency of the objective findings with the patient’s
reported medical history would suggest that further investigation is
warranted. This should include a review of the patient’s pre-existing
condition, potential use of medications prescribed for her condition,
other compounds she may have been consuming, and the status of her
health prior to the reported incident. In the absence of the
aforementioned data, the exclusion of possible differential diagnoses is
not well-supported.

Case 3 describes a 53-year-old
female who developed symptoms of painless jaundice and pruritus 3 wk
prior to presenting at the hospital[1].
This patient denied family history of liver disease, but no discussion
was provided regarding her own medical history, other than the fact that
she reportedly denied the use of alcohol and did not engage in “illicit
substance abuse”. The authors further stated that the patient had not
been prescribed any new medications, which implies that she may have
been taking other agents concomitantly. However, information regarding
the use of concomitant medications, or the conditions for which she may
have been receiving treatment, was not disclosed. Such information is
critical and should have been obtained through follow-up review of the
patient’s previous medical records. Without this information, it is
unknown whether concomitant medication(s) were withdrawn and/or
accounted for during the dechallenge process. The patient’s use of
Herbalife products was also not specified by product names and it is
unknown whether the dosage and frequency of consumption was adherent to
recommendations indicated on the product label(s). In addition to the
absence of the aforementioned pertinent patient data, there are various
refutable facts that remain in regard to the comments and conclusions
made by the authors.

In their WJH article, the
authors concluded that it was difficult to isolate a single ingredient
or mechanism associated with acute liver injury for either patient
consuming Herbalife products[1].
In an effort to discuss potential causative agents for the reported
conditions in these patients, the authors extraneously reference
previously published case reports involving Herbalife products,
including those of two consumers who reportedly developed hepatotoxicity
following exposure to Bacillus subtilis (B. subtilis)[2].

In
review of this reference, it has been noted that there were various
critical deficiencies in the scientific methodology used to isolate B. subtilis
in the Herbalife samples reported to have been contaminated. For
example, a dose dependent increase in LDH leakage in HepG2 cells was
observed in the experimental assay, but investigators did not present
any control data for their experiments, nor did they present any data
that suggested this assay is a valid proxy for liver injury in healthy
individuals “in vivo”. Neither patient reported symptoms consistent with classical B. subtilis
food poisoning and they did not report testing the product for the
detection of cerulide or any of the reported heat-stable toxins
associated with certain strains of B. subtilis. Furthermore, the investigators did not enumerate the levels of B. subtilis
in the products tested or report testing relevant specimens from the
patients for these organisms or their toxins. This was a crucial step
missing in the reported investigation as all previous documented reports
find that high levels of the organism must be consumed to cause
illness. Herbalife products, consumed by the patients described in the WJH article, to date show no evidence of B. subtilis contamination. B. subtilis
infections are relatively rare and seldom contracted through food
sources. This bacterium is actually ubiquitous in nature and generally
recognized as safe with a history of safe use in food, and is considered
to be safe for the production of enzymes or ingredients for use in
food[3]. There have been reported cases of B. subtilis-related
gastroenteritis and other complications, usually involving
immuno-compromised patients or those with other underlying chronic
illnesses, which did not appear to be the case for any of the patients
presented in the WJH article. Therefore, it is highly unlikely that B. subtilis
could be the cause or have contributed to the severe hepatotoxicity of
patients in either the referenced article or the two patients discussed
in the WJH article.

The WJH authors
also suggest intentional or incidental contamination of Herbalife
ingredients and identify various potential sources, including unrefined
raw herbal extracts, heavy metals, pesticides, and additives[1].
However, some of the additives mentioned as potential contaminants by
the authors (e.g., flavoring, colors, and preservatives) are commonly
used and well-documented industry-wide as safe for consumption in
conventional foods, as well as dietary supplements,. In addition,
authors also reference an article from 2002 that reviews possible
contamination sources inherent to herbal remedies marketed without
proper quality control measures in place[5].
Herbalife is not specifically implicated in the referenced article, yet
the authors imply that Herbalife product contamination and lack of
quality control contributed to the liver injury. The authors’ assumption
is wrong and does not take into consideration that the United States
FDA requires dietary supplement manufacturers to use current Good
Manufacturing Practices (cGMPs) in the production of dietary
supplements[4].
The goal of these regulations is to “ensure that a dietary supplement
contains what the manufacturer intends” and meets specifications to
ensure the dietary supplement contains the correct ingredient, purity,
strength and composition intended. Herbalife has rigorous processes in
place concerning quality control, including extensive safety reviews
based on existing literature for product ingredients, testing to confirm
that labeled ingredients are present in finished goods, and to assure
all tested ingredients meet product specifications on an ongoing basis.
In addition to complying with cGMP regulations, Herbalife acts in
accordance with other generally recognized industry standards or
requirements by sourcing and testing raw materials to further ensure
that the final product complies with specifications for identity,
purity, potency and contaminants.

The authors also try to implicate the Camellia sinensis (C. sinensis) used in Herbalife’s tea drink products by citing case reports of liver injury in association with ethanolic extracts of C. sinensis, which contain a concentrated fraction of EGCG[1].
The most important safety consideration for green tea is the extraction
method. The historical data supporting the safety of green tea is based
on the consumption of an aqueous extract over thousands of years,
specifically, the typical three cups per day that are commonly consumed
in Asian countries. Aqueous extracts of green tea are quite different
from solvent extractions, which are commonly used to concentrate select
fractions of green tea, such as EGCG or caffeine. Again, the WJH
authors have not considered the clinical significance of potential
differences in raw material processing amongst manufacturers, controls
for contamination and identification of raw materials, and the
implication of these differences when reviewing published case reports
of liver injury. In addition, the authors state that Herbalife has
refused to provide detailed analyses of ingredients and formulations,
although no attempt was made by these authors to contact Herbalife to
obtain further information regarding Herbalife products or ingredients.
Herbalife has, to date, remained compliant with all formal regulatory
requests and requirements for product information.

The authors state that significant liver injury induced by herbal supplements is a rare event[1].
This statement is true as approximately 20 to 50 percent of all cases
presenting as hepatotoxicity are cryptogenic leading to the incidental
association of liver disease with a group of products in the absence of
specific evidence[5].
While this disease is the most common cause of drug withdrawal during
post-marketing surveillance, it is an uncommon cause of liver disease.
The background incidence of hepatotoxicity in populations is clearly
comparable to the reported incidence of immunoallergic and
individualistic reactions to allergens in foods, supplements, or the
environment. For example, in a study of 71 000 North Americans in 1992,
the background rate of idiopathic or cryptogenic liver disease was 24
cases per 100 000 individuals compared to 14 per 100 000 attributed to
cases of hepatitis B, 25 per 100 000 due to alcoholism, and 7 per
100 000 to other viral illnesses[6].
While the spectrum of liver diseases may well have changed since 1992
when this survey was done, idiopathic liver disease remains a
significant percentage of all cases. Therefore, it is particularly
important in making such associations to have incontrovertible evidence
such as is often available for prescription drugs where, under
controlled conditions, a cause-effect relationship can be established.

Finally,
the authors also state that existing case reports of dietary
supplement-induced hepatotoxicity include patients with pre-existing
liver disease and that weight loss supplements could worsen such
conditions in these patients. However, this effect could occur from many
different substances, including over-the-counter and prescription
medications, as these patients may be “pre-sensitized” due to an
underlying hepatic condition.

In conclusion, the
reference to Herbalife products as contaminated and generally comparable
to all dietary supplements or weight loss products is not
scientifically supported. Further information regarding patient
histories, concomitant medications and other compounds, dechallenge
results, and product specifications and usage is indicated to assess
fully the association of Herbalife products in the WJH case
reports. Therefore, the article does not objectively support a causal
relationship between the reported cases of liver injury and Herbalife
products or ingredients.

Multiple
medical resources have found that there are 2,000,000 people around the
world who are offering products that may make you very sick.

Herbalife
is a publicly traded company based out of Los Angeles, California.
Since 1980 it has allowed people the opportunity to become independent
sales reps with the opportunity to lead others to do the same in the
form of multi-level marketing, or network marketing.Like any large organization with several decades of experience, there
are some controversies behind this one. For example, in 1986, the state
of California claimed that the company made inflated claims regarding
income potential for which Herbalife settled for $850,000, and in 2004
thousands of current and former distributors took the company to court
on the grounds of running a pyramid scheme. Herbalife settled the latter case for $6,000,000 (less than $700 each).Along with these legal matters are much more pressing health
concerns. Several medical resources have found that Herbalife products
may actually cause hepatitis.What is Hepatitis and How is it Caused?Hepatitis can be characterized as an inflammation of the liver. One
visible symptom is jaundice, and less visible ones are lack of appetite
and a feeling of overall discomfort.Hepatitis is typically caused by a virus, but it can also be caused
by toxins when taken regularly, such as alcohol or an infection that is
already present. The question on many people's minds regarding Herbalife
products would be, how could these products be linked to infecting
those who take them?The answer is in the ingredients. There has to be something toxic in
some or all of the products released by the company, but it is hard to
know which ones because the FDA does not regulate herbal supplements the
same way it does medicine. This is why athletes find out via heart
attack that ephedrine is not so great, and how health conscious people
discover that they may be poisoning themselves the hard way, as reported
in a 2007 article published in The Journal of Hepatology titled "Herbal Does not Mean Innocuous."Countries That Have Reported Illness Links to HerbalifeIt is important to note where the sources are that have reported on
Herbalife. This is because some people go on the attack against
networking companies because they think they are dangerous or terrible,
and some governments are anti-capitalistic, so they would be against a company like Herbalife because they do not want their people to have too much freedom and control.In 2004, 12 patients in Israeli hospitals with severe liver problems
had one thing in common. They were taking an Herbalife supplement that
aided digestion. When their liver enzymes normalized, they resumed their
normal regimen of the product and were sick again.The 2007 article noted from the European Journal of Hepatology had
several sources, one of which was medical professionals from
Switzerland. In it, the ten most severe cases covered showed two
patients with "certain causality" while the other eight had "probable
causality." The duration of the illness ranged from two months to twelve
years.The objective here is not to demonize a company or industry, but to
alert consumers that when Herbalife distributors pitch the quality of
their products, they may be pitching high-end hepatitis. And while the
ingredients linked to causing disease in the past may have been rid of,
it does not mean that today's products are safe.Without FDA interaction, humans are the test subjects for herbal
supplements. The best way to go when it comes to supplements is to use
one with a long track record of not hurting its users.Jan. 5 update from the author: On December 23,
George Fischer and one of his doctors had a conference call with me.
During the course of that conversation, they promised that they would
send me information contradicting the reporting in the Journal of
Hepatology. No such contact has been made since.

Herbal
Life is a company that produces a wide range of nutrition products,
from vitamin supplements and diet pills to protein snacks and digestive
health supplements. While these supplements may be beneficial to your
health, you should research the ingredients in each supplement to avoid
possible side effects. Even if a product has positive reviews, your
results may vary. Consult your doctor before using any Herbal Life
supplements to discuss their safety and efficacy.

Hypotension: Cell-U-LossCell-U-Loss
is a supplement marketed by Herbal Life to help you decrease bodily
fluid retention. This product contains a number of ingredients, most of
them herbs. One herb in the Cell-U-Loss formula is hydrangea, which may
cause hypotension, or low blood pressure, according to the Silberg
Center for Dental Science. Hypotension is a condition that may cause
fainting, shock and dizziness. The Silberg Center notes that hydrangea
may be especially dangerous when used in conjunction with high blood
pressure medication.

Cancer Risk: Total Control

Total
Control is a weight management supplement that is intended to increase
your metabolism, increase your energy levels, and promote healthy weight
loss. Total Control is similar to many other weight loss supplements
because it contains stimulants such as caffeine and yerba mate.
According to Katherine Zeratsky, R.D., L.D., yerba mate may promote
weight loss, but it also has a number of side effects--including
increased cancer risk. According to Zeratsky, regular intake of yerba
mate may increase your risk of cancers such as those of the lungs, mouth
and esophagus. Zeratsky does note that the risk is probably small,
however.

Difficulty Sleeping: LiftOff

LiftOff
is an energy supplement produced by Herbal Life. This product comes in
the form of a tablet that dissolves in water. LiftOff contains a number
of stimulants to increase energy, but these ingredients may also cause
side effects, including difficulty sleeping, or insomnia. Herbal Life
LiftOff contains caffeine, a common stimulant that may cause sleeping
problems, according to the University of Maryland Medical Clinic. In
addition, LiftOff contains guarana, which the website Drugs.com explains
may cause anxiety, nervousness and trouble sleeping. Due to these side
effects, you should not take LiftOff within several hours of bed time.

In the Niteworks group, anaerobic threshold significantly increased
17% at week 1, and the effect was significantly sustained by week 3.

In the placebo group, there was no change in anaerobic threshold.

The anaerobic threshold for the Niteworks group was significantly higher vs placebo at week 1 and week 3.

There were no significant changes in VO2 max (a measure of aerobic
capacity) between placebo and Niteworks groups at either week 1 or 3
when compared to the start of the study.

There were no side effects in either group.

The bottom line?The authors concluded, “An arginine and antioxidant-containing
supplement increased the anaerobic threshold at both week one and week
three in elderly cyclists. No effect on VO2 max was observed. This study
indicated a potential role of L-arginine and antioxidant
supplementation in improving exercise performance in elderly.”It’s not stated in the study whether aside from positive changes in
anaerobic threshold there were clinically meaningful benefits. Does a
17% change result in better quality of life, greater activities of daily
living, etc.?More background on arginine and exercise performance is here.NOTE: The study, conducted at UCLA and funded by Herbalife, used
Herbalife’s original formula Niteworks. The current product has a
slightly different formula, although no changes were made to the active
ingredients, according to the article published on Medical News Today.

In the Niteworks group, anaerobic threshold significantly increased
17% at week 1, and the effect was significantly sustained by week 3.

In the placebo group, there was no change in anaerobic threshold.

The anaerobic threshold for the Niteworks group was significantly higher vs placebo at week 1 and week 3.

There were no significant changes in VO2 max (a measure of aerobic
capacity) between placebo and Niteworks groups at either week 1 or 3
when compared to the start of the study.

There were no side effects in either group.

The bottom line?The authors concluded, “An arginine and antioxidant-containing
supplement increased the anaerobic threshold at both week one and week
three in elderly cyclists. No effect on VO2 max was observed. This study
indicated a potential role of L-arginine and antioxidant
supplementation in improving exercise performance in elderly.”It’s not stated in the study whether aside from positive changes in
anaerobic threshold there were clinically meaningful benefits. Does a
17% change result in better quality of life, greater activities of daily
living, etc.?More background on arginine and exercise performance is here.NOTE: The study, conducted at UCLA and funded by Herbalife, used
Herbalife’s original formula Niteworks. The current product has a
slightly different formula, although no changes were made to the active
ingredients, according to the article published on Medical News Today.4/11/10 20:31 JR